VX-702 is an orally-available, aminopyridine-based, ATP-competitive inhibitor of p38 MAPK with a Kd of 3.7 nM and 17 nM at 10 uM for p38a and p38b, respectively. [1] In an ex vivo blood assay primed with LPS< VX-702 dose-dependently inhibited the production of IL-6, IL-1b, TNFa at IC50 of 59, 122, and 99 ng/mL, respectively. [2] VX-702 was found to be equivalent to prednisolone and methotrexate in a mouse collagen-induced arthritis model.

Clinical efficacy models plus transient suppression of inflammation biomarkers suggest that p38 MAPK inhibition by agents such as VX-702 may not be a viable approach to the treatment of chronic inflammation in RA. [3]